Superoxide production and oxygen consumption in endothelium-intact and -denuded artery stimulated by angiotensin II

Arteries stimulated by angiotensin II (AII) to contract do not display the expected augmentation of O₂ consumption seen with other cardiovascular contractile agonists. We tested the hypothesis that superoxide (O₂⁻) or other reactive oxidant species generated by AII played a role in the paradoxical O₂ consumption response in porcine carotid artery, with or without an intact endothelium. Endothelium-denuded arteries were incubated with either 1 μM diphenylene iodonium (DPI), an inhibitor of NAD(P)H oxidase, 300 u/ml superoxide dismutase (SOD), a scavenger of O₂⁻, or 20 U/ml catalase, an enzyme which promotes conversion of O₂⁻ (scavenged in the form of H₂O₂) to O₂. DPI treatment resulted in the expected increase in O₂ consumption upon contractile activation with AII challenge (1.05± 0.23 μmol/g/min; n = 6, p < .01), as did treatment with SOD (0.67± 0.20 μmol/g/min; n = 4, p < .05). Catalase incubation resulted in a burst of O₂ generation upon AII challenge (1.30 ± 0.21 μmol/g/min; n = 10, p < .001). In endothelium-intact arteries, O₂ consumption was again not augmented with AII challenge; instead, a burst of O₂ production was observed (0.66 ± 0.22 μmol/g/min; n = 9, p < .05), which was not affected further by addition of catalase. Thus, the absence of apparent augmentation of O₂ consumption during contractile activation of endothelium-denuded arteries was attributed to simultaneous NAD(P)H oxidase-dependent production of O₂⁻, and attendant H₂O₂ and O₂ generation which either and masked the detection of O₂ consumed or suppressed mitochondrial uptake of O₂, or both. An intact endothelium was required to manifest the burst of O₂ generation with AII stimulation under normal conditions. (Mol Cell Biochem xxx: 235–239, 2005)